A Randomised, Double-blind, Placebo-controlled Trial to Assess Safety, Tolerability and Pharmacokinetics of Liraglutide in Obese Adolescent Subjects Aged 12 to 17 Years

This trial is conducted in Europe. The purpose of the trial is to assess safety, tolerability and pharmacokinetics (the exposure of the trial drug in the body) of liraglutide in obese adolescent subjects aged 12 to 17 years.

Study Overview

• Status: Completed
• Conditions: Obesity; Metabolism and Nutrition Disorder
• Intervention / Treatment: Drug: liraglutide; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Hannover, Germany, 30173
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Subjects with Tanner stage 2-5 pubertal development at time of randomisation
• Body Mass Index (BMI) corresponding to 30 kg/m^2 or above for adults by international cut-off points and 45 kg/m^2 or below and equal to or above 95th percentile for age and gender
• Fasting plasma glucose below 7.0 mmol/L (126 mg/dL) (central laboratory analysis)

Exclusion Criteria:

• Subjects with clinically diagnosed secondary causes of childhood obesity such as chromosomal abnormalities (e.g. Turner syndrome), syndromic obesity (e.g. Prader Willi syndrome) or endocrinologic disorders (e.g. Cushing Syndrome)
• Subjects with confirmed diagnosis of bulimia
• Subjects with Tanner stage 1 development (prepubertal)
• Diagnosis of type 1 or type 2 diabetes mellitus as judged by the investigator
• Previous treatment with a GLP-1 (glucagon-like peptide 1) receptor agonists (e.g. exenatide or liraglutide or other), DPP-4 (dipeptidyl peptidase-4) inhibitors, orlistat or other weight lowering medication, any antipsychotic medication or systemic corticosteroids within the last 3 months
• Currently using or have used within 3 months before screening for this trial: any systemic treatment that in the opinion of the investigator interferes with PK (pharmacokinetic), PD (pharmacodynamic) and safety endpoints
• Surgical treatment for obesity
• Past or current chronic or idiopathic pancreatitis, or any of the following: -amylase or lipase above 2 times UNR (upper normal range), -triglycerides above 500 mg/dL, -calcium above UNR, -history of gallstones (not treated by cholecystectomy)
• Uncontrolled treated or untreated hypertension 99th percentile for age and gender in children
• History of major depressive disorder or history of other severe psychiatric disorders (e.g. schizophrenia or bipolar disorder) that could in the opinion of the investigator interfere with trial compliance or subject safety
• Subjects with a history of suicide attempts or history of any suicidal behaviour within the past month before entry into the trial

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: placebo; Administered subcutaneously (s.c., under skin) for 5-6 weeks. Initial dose of 0.6 mg/day. The dose will be escalated by 0.6 mg/day in weekly steps to a maximum of 3.0 mg/day
Experimental: Liraglutide	Drug: liraglutide; Administered subcutaneously (s.c., under skin) for 5-6 weeks. Initial dose of 0.6 mg/day. The dose will be escalated by 0.6 mg/day in weekly steps to a maximum of 3.0 mg/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Number of treatment emergent adverse events (TEAEs)	From the time of first dosing (Day 0) and until completion of follow-up visit (up to 6 weeks' treatment and 5-14 days subsequent follow-up period)

Secondary Outcome Measures

Outcome Measure	Time Frame
Incidence of liraglutide antibody	At follow-up (up to 6 weeks' treatment and 5-14 days subsequent follow-up period)
At steady state at each dose step: C-trough	After 7, 14, 21, 28 and 35 days of treatment
At steady-state: model-derived area under the liraglutide concentration curve over the dosing	Last dose day, after up to 6 weeks' treatment
At steady-state: model-derived t½ (terminal half-life)	Last dose day, after up to 6 weeks' treatment
At steady-state: model-derived CL/F (apparent clearance)	Last dose day, after up to 6 weeks' treatment
At steady-state: model-derived V/F (apparent volume of distribution)	Last dose day, after up to 6 weeks' treatment

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Danne T, Biester T, Kapitzke K, Jacobsen SH, Jacobsen LV, Petri KCC, Hale PM, Kordonouri O. Liraglutide in an Adolescent Population with Obesity: A Randomized, Double-Blind, Placebo-Controlled 5-Week Trial to Assess Safety, Tolerability, and Pharmacokinetics of Liraglutide in Adolescents Aged 12-17 Years. J Pediatr. 2017 Feb;181:146-153.e3. doi: 10.1016/j.jpeds.2016.10.076. Epub 2016 Dec 13.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: February 8, 2013
• First Submitted That Met QC Criteria: February 8, 2013
• First Posted (Estimate): February 11, 2013

Study Record Updates

• Last Update Posted (Estimate): December 22, 2016
• Last Update Submitted That Met QC Criteria: December 21, 2016
• Last Verified: December 1, 2016

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nutrition Disorders; Hypoglycemic Agents; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: NN8022-3967; 2012-000038-20 (EudraCT Number); U1111-1126-8119 (Other Identifier: WHO)